Urine and oral fluid drug testing in support of pain management.

In recent years, the abuse of opioid drugs has resulted in greater prevalence of addiction, overdose, and deaths attributable to opioid abuse. The epidemic of opioid abuse has prompted professional and government agencies to issue practice guidelines for prescribing opioids to manage chronic pain. An important tool available to providers is the drug test for use in the initial assessment of patients for possible opioid therapy, subsequent monitoring of compliance, and documentation of suspected aberrant drug behaviors. This review discusses the issues that most affect the clinical utility of drug testing in chronic pain management with opioid therapy. It focuses on the two most commonly used specimen matrices in drug testing: urine and oral fluid. The advantages and disadvantages of urine and oral fluid in the entire testing process, from specimen collection and analytical methodologies to result interpretation are reviewed. The analytical sensitivity and specificity limitations of immunoassays used for testing are examined in detail to draw attention to how these shortcomings can affect result interpretation and influence clinical decision-making in pain management. The need for specific identification and quantitative measurement of the drugs and metabolites present to investigate suspected aberrant drug behavior or unexpected positive results is analyzed. Also presented are recent developments in optimization of test menus and testing strategies, such as the modification of the standard screen and reflexed-confirmation testing model by eliminating some of the initial immunoassay-based tests and proceeding directly to definitive testing by mass spectrometry assays.

Interpretation of urine drug testing results in patients using transdermal buprenorphine preparations for the treatment of chronic noncancer pain.

OBJECTIVE: To determine whether the prevailing liquid chromatography and tandem mass spectroscopy assay (LC-MS/MS) assay designed to monitor buprenorphine compliance of the sublingual formulation used in the substance abuse treatment setting can be extrapolated to the transdermal formulation used in the chronic pain treatment setting, which is 1000-fold less concentrated. DESIGN: Retrospective chart review. SUBJECTS: Self-reported compliant patients using the transdermal or sublingual formulations of buprenorhphine. Transdermal patch application was also visually confirmed during clinic visits. METHODS: Urine drug test results from a LC-MS/MS were compared between samples from transdermal and sublingual patients. RESULTS: While all sublingual patients tested positive for at least one metabolite of buprenorphine, only 69% of the transdermal patients did so. In addition, the most abundant metabolite in the transdermal patients was buprenorphine-glucuronide, as compared with norbuprenorphine-glucuronide in sublingual patients. CONCLUSIONS: These data suggest that currently available urine drug tests for buprenorphine, including the more expensive LC-MS/MS based assays, may not be sufficiently sensitive to detect the metabolites from transdermal buprenorphine patients. This study highlights the need to evaluate the value and sensitivity of urine drug tests given the wide range of buprenorphine dosing in clinical practice. These results underscore the need for additional cost benefit analyses comparing different confirmatory drug testing techniques including many commercially available drug testing options. © 2014 Wiley Periodicals, Inc.

Prevalence of 25-hydroxyvitamin D2 in Western New York: a 3-year study.

BACKGROUND: We evaluated the distribution of 25OH-D2 and 25OH-D3 in a general patient population in Western New York to provide insights into how common detectable vitamin D2 is among samples from a general patient population. METHODS: Serum 25OH-D2 and 25OH-D3 results measured by LC-MS/MS from June 2009 to December 2012 were retrospectively analyzed. RESULTS: A total of 266,269 serum tests were included for analysis. The percentage of tests with 25OH-D2 levels above the assay limit of quantitation (LoQ) decreased from 32% to 17% over the course of the study period. The percentage of tests with 25OH-D2 levels higher than those of 25OH-D3 decreased from 21% to 12%. Sixty-seven percent of the test results with 25OH-D2 levels above the LoQ had serum concentrations of 25OH-D2 higher than those of 25OH-D3. CONCLUSION: Prevalence of tests with quantifiable 25OH-D2 decreased over time and yet 17% of them still had detectable levels of 25OH-D2, 67% of which had 25OH-D2 levels higher than 25OH-D3. To achieve accurate 25-hydroxyvitamin D measurement, clinical laboratories should assess the accuracy of their assays, and if necessary, determine the local prevalence of 25OH-D2 to determine if mass spectrometry is the platform of choice to assess vitamin D deficiency.

The opioid abuse and misuse epidemic: implications for pharmacists in hospitals and health systems.

PURPOSE: The current epidemic of prescription opioid abuse and misuse in the United States is discussed, with an emphasis on the pharmacist's role in ensuring safe and effective opioid use. SUMMARY: U.S. sales of prescription opioids increased fourfold from 1999 to 2010, with an alarming rise in deaths and emergency department visits associated with the use of fentanyl, hydrocodone, oxycodone, and other opioid medications. Signs and symptoms of opioid toxicity may include altered mental status, hypoventilation, decreased bowel motility, central nervous system and respiratory depression, peripheral vasodilation, pulmonary edema, hypotension, bradycardia, and seizures. In patients receiving long-term opioid therapy for chronic pain, urine drug testing is an important tool for monitoring and assessment of therapy; knowledge of opioid metabolic pathways and assay limitations is essential for appropriate use and interpretation of screening and confirmatory tests. In recent years, there has been an increase in federal enforcement actions against pharmacies and prescription drug wholesalers involved in improper opioid distribution, as well as increased reliance on state-level prescription drug monitoring programs to track patterns of opioid use and improper sales. Pharmacies are urged to implement or promote appropriate guidelines on opioid therapy, including the use of pain management agreement plans; policies to ensure adequate oversight of opioid prescribing, dispensing, and waste disposal; and educational initiatives targeting patients as well as hospital and pharmacy staff. CONCLUSION: Pharmacists in hospitals and health systems can play a key role in recognizing the various forms of opioid toxicity and in preventing inappropriate prescribing and diversion of opioids.

Utilization management in toxicology.

Recent upward trends in the prevalence of abuse of prescription drugs and illicit substances have resulted in increased demands for toxicology testing to support the emergency department and drug treatment in pain management programs. This review will discuss the challenges faced by clinical laboratories to manage the utilization of toxicology tests, particularly those ordered in managing poisoned patients in the emergency department and chronic pain patients on opioid therapy. Optimal utilization of toxicology tests to support the emergency department relies on selecting the appropriate tests for the patient, and the availability of the results in a timely fashion. Two tiers of toxicology testing systems with different requirements for turnaround time will be discussed. In patients with chronic pain urine drug testing, including screening and confirmation testing are used extensively in pain management to monitor patient compliance. A thorough understanding of the performance characteristics of the test methodologies and drug metabolism is a key to making a proper analytical and clinical interpretation of the test results and will contribute to effective utilization of these tests. In addition, the reimbursement system is an important factor in the decision making process for test selection utilization as significant costs can be incurred by both payers and patients. Collaboration, trust, and effective communication among clinicians, patients, and clinical laboratory professionals are essential for effective utilization of toxicology testing.

Label-free porous silicon immunosensor for broad detection of opiates in a blind clinical study and results comparison to commercial analytical chemistry techniques.

In this work, we evaluate for the first time the performance of a label-free porous silicon (PSi) immunosensor assay in a blind clinical study designed to screen authentic patient urine specimens for a broad range of opiates. The PSi opiate immunosensor achieved 96% concordance with liquid chromatography-mass spectrometry/tandem mass spectrometry (LC-MS/MS) results on samples that underwent standard opiate testing (n = 50). In addition, successful detection of a commonly abused opiate, oxycodone, resulted in 100% qualitative agreement between the PSi opiate sensor and LC-MS/MS. In contrast, a commercial broad opiate immunoassay technique (CEDIA) achieved 65% qualitative concordance with LC-MS/MS. Evaluation of important performance attributes including precision, accuracy, and recovery was completed on blank urine specimens spiked with test analytes. Variability of morphine detection as a model opiate target was <9% both within-run and between-day at and above the cutoff limit of 300 ng mL(-1). This study validates the analytical screening capability of label-free PSi opiate immunosensors in authentic patient samples and is the first semiquantitative demonstration of the technology's successful clinical use. These results motivate future development of label-free PSi technology to reduce complexity and cost of diagnostic testing particularly in a point-of-care setting.

Interpretation and utility of drug of abuse immunoassays: lessons from laboratory drug testing surveys.

CONTEXT: To assist with patient diagnosis and management, physicians from pain services, drug treatment programs, and the emergency department frequently request that urine be tested for drugs of abuse. However, urine immunoassays for drugs of abuse have limitations. OBJECTIVE: To use data from the College of American Pathologists Proficiency Testing Surveys to determine and summarize the characteristics, performance, and limitations of urine immunoassays for drugs of abuse. DESIGN: Six years of urine drug testing proficiency surveys were reviewed. RESULTS: Lysergic acid diethylamide and methaqualone are infrequently prescribed or abused and, therefore, testing may be unnecessary. However, implementation of more specific testing for methylenedioxymethamphetamine and oxycodone may be warranted. Each drug of abuse immunoassay exhibits a different cross-reactivity profile. Depending on the cross-reactivity profile, patients with clinically insignificant concentrations of drugs may have false-positive results, and patients with clinically significant concentrations of drugs may have false-negative results. CONCLUSIONS: Laboratory directors should be aware of the characteristics of their laboratories' assays and should communicate these characteristics to physicians so that qualitative results can be interpreted more accurately. Furthermore, manufacturer's claims should be interpreted with caution and should be verified in each organization's patient population, if possible.

Pharmacokinetics and pharmacodynamics of methylecgonidine, a crack cocaine pyrolyzate.

Methylecgonidine is formed from cocaine base when smoked and has been identified in biological fluids of crack smokers. Ecgonidine, a metabolite of methylecgonidine formed via esterase activity, also has been identified in similar samples collected from crack smokers. Methylecgonidine and ecgonidine can be used as biomarkers to differentiate smoking from cocaine use via other routes of administration. We determined the pharmacokinetic properties of methylecgonidine and ecgonidine in sheep after intravenous administration of methylecgonidine at doses of 3.0, 5.6, and 10.0 mg/kg using gas chromatography-mass spectrometric assays. Methylecgonidine clears quickly from blood with a half-life of 18 to 21 min, whereas ecgonidine has a longer half-life of 94 to 137 min. Because ecgonidine clears more slowly, it may be a more effective biomarker of cocaine smoking. The cardiovascular stimulant effects of cocaine contrast with reported in vitro muscarinic agonist effects of methylecgonidine, decreasing contractility and stimulating nitric oxide production in cardiac cells and tissues. To test the hypothesis that methylecgonidine produces cardiovascular effects in vivo consistent with muscarinic agonism, methylecgonidine was administered to sheep intravenously (0.1-3.0 mg/kg) while monitoring heart rate and blood pressure. Significant hypotension and tachycardia occurred in all three sheep. Two of the three sheep demonstrated mild bradycardia 3 to 5 min after methylecgonidine injection. Intravenous pretreatment with atropine methyl bromide (15 microg/kg) antagonized methylecgonidine-induced hypotension in all three sheep, supporting the hypothesis that methylecgonidine acts as a muscarinic agonist in vivo.

National academy of clinical biochemistry laboratory medicine practice guidelines: recommendations for the use of laboratory tests to support poisoned patients who present to the emergency department.

BACKGROUND: Exposure to drugs and toxins is a major cause for patients' visits to the emergency department (ED). METHODS: Recommendations for the use of clinical laboratory tests were prepared by an expert panel of analytical toxicologists and ED physicians specializing in clinical toxicology. These recommendations were posted on the world wide web and presented in open forum at several clinical chemistry and clinical toxicology meetings. RESULTS: A menu of important stat serum and urine toxicology tests was prepared for clinical laboratories who provide clinical toxicology services. For drugs-of-abuse intoxication, most ED physicians do not rely on results of urine drug testing for emergent management decisions. This is in part because immunoassays, although rapid, have limitations in sensitivity and specificity and chromatographic assays, which are more definitive, are more labor-intensive. Ethyl alcohol is widely tested in the ED, and breath testing is a convenient procedure. Determinations made within the ED, however, require oversight by the clinical laboratory. Testing for toxic alcohols is needed, but rapid commercial assays are not available. The laboratory must provide stat assays for acetaminophen, salicylates, co-oximetry, cholinesterase, iron, and some therapeutic drugs, such as lithium and digoxin. Exposure to other heavy metals requires laboratory support for specimen collection but not for emergent testing. CONCLUSIONS: Improvements are needed for immunoassays, particularly for amphetamines, benzodiazepines, opioids, and tricyclic antidepressants. Assays for new drugs of abuse must also be developed to meet changing abuse patterns. As no clinical laboratory can provide services to meet all needs, the National Academy of Clinical Biochemistry Committee recommends establishment of regional centers for specialized toxicology testing.

Organophosphate pesticides: biochemistry and clinical toxicology.

Organophosphate pesticides are used extensively worldwide, and poisoning by these agents, particularly in developing nations, is a serious public health problem. The toxicokinetics and toxicodynamics of organophosphate poisoning vary not only with the route and extent of exposure, but also the chemical structure of the agent. The mechanism of toxicity is the inhibition of acetylcholinesterase, resulting in an accumulation of the neurotransmitter acetylcholine and the continued stimulation of acetylcholine receptors. The standard treatment consists of reactivation of the inhibited acetylcholinesterase with an oxime antidote and reversal of the biochemical effects of acetylcholine with atropine. Patients who receive treatment promptly usually recover from acute toxicity but may suffer from neurologic sequelae.